Low CD3 level is a risk factor for amyotrophic lateral sclerosis: a Mendelian randomization study

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease characterized by neuronal degeneration of the spinal cord and brain and believed to be related to the immune system. In this study, our aim is to use Mendelian randomization (MR) to search for immune markers related to ALS. A total of 731 immune cell traits were included in this study. MR analysis was used to identify the causality between 731 immune cell traits (with 3,757 Europeans) and ALS (with 138,086 Europeans). Colocalization analysis was used to verify the found causality, protein-protein interaction prediction was used to look for the interacting proteins that are known to be involved in ALS. We found low expression levels of CD3 on central memory CD8+ T cell is risk factor for ALS (OR = 0.90, 95% CI: 0.86-0.95, P = 0.0000303). CD3 can interact with three ALS-related proteins: VCP, HLA-DRA and HLA-DRB5, which are associated with adaptive immune response. Our study reported for the first time that low-level CD3 is a risk factor for ALS and the possible mechanism, which could provide a potential strategy for ALS diagnosis and therapy.